Thiophene derivatives of formula (I), which is set forth below, may be converted into the vitamin (.+-.)-biotin by hydrogenation under suitable conditions. Suitable conditions for the catalytic hydrogenation are described in "Helvetica Chimica Acta", 59 (1976), page 1 005, as well as in DE-OS 30 18 109.
Further, it is known to react compounds of the formula (II), which is set forth below, with thioacetic acid, thiourea, thiourea acyl compounds or with sodium thiosulphate, to form S-containing intermediate products of the formula ##STR4## wherein R.sub.3 is lower alkyl, R.sub.4 and R.sub.5 are lower acyl and Z is one of the residues described below.
The said S-containing intermediate products of formula IV, where Z=CH.sub.3 CO-- (thioacetate), may be prepared according to a process described by Taguchi et al in "Chemistry Letters" (1974), pages 729 to 730.
Intermediate products of formula (IV), where Z=C(.dbd.NH)--NH.sub.2 .multidot.HBr (thiourea), may also be prepared according to a process described by Isaka et al in "Yakugaku Zasshi", 88 (4) (1968), pages 422 to 427. Intermediate products of formula (IV), where Z=C(.dbd.NH)--NHCOPh.multidot.HBr (benzoylthiourea) and Z=--SO.sub.2 --O--Na (thiosulphate), may be prepared, as described by Zavyalov et al in "Izvestia Akademia Nauk. SSSR Ser. Chim. (1980), pages 1 943 to 1 945. According to Taguchi et al. (cf. "Chemistry Letters" (1974), pages 729 to 730) the intermediate product of formula (IV), where Z=CH.sub.3 CO--, is first subjected to alkaline hydrolysis to form an intermediate product of formula IV, where Z=H, and thereafter to intramolecular cyclisation in a mineral acidic medium to form the thiophene derivative of formula (I). The isothiuronium salt prepared from Isaka et al. (cf. Yakugaku Zasshi, 88 (4) (1968), pages 422 to 427) is also first subjected to alkaline hydrolysis and thereafter to intramolecular cyclisation in a mineral acidic medium to the thiophene derivative of formula (I). The intermediate products of formula IV may be converted into thiophene derivatives of formula (I) in an acidic medium in one step by hydrolysis and intramolecular cyclisation (cf. Zavyalov et al in "Izvestia Akademia Nauk. SSSR Ser. Chim." (1980), pages 1 943 to 1 945, SSSR-patent 579 767 and PCT application WO 86/02069).
However, when re-working the above mentioned processes for the preparation of thiophene derivates of formula (I), it has been found that these processes are not suited for the technical production on a large scale, in particular for an industrial performance, since they have a number of severe disadvantages:
(1) The 1,3-diacyl-4-halomethyl-5-(5-alkoxycarbonylpentanoyl)-4-imidazole-2-one of formula (II) used as a starting product is prepared by halogenation of the compound of formula (V) ##STR5## wherein R.sub.3, R.sub.4 and R.sub.5 have the significances given above (cf. Duschinsky and Dolan in "Am. Soc." 70 (1948), pages 657 to 662).
The crude halogenation product of formula (II) obtained thereby has to be brought to a high degree of purity by recrystallization before it can be reacted according to known processes. Without this prepurification, in the course of the subsequent chemical reaction by-products are formed, which are extremely difficult to separate and which result in an early poisoning of the noble metal catalysts in the catalytic hydrogenation of the thiophene derivatives of formula (I) obtained in a decrease of the yiled of (.+-.)-biotin;
(2) The S-containing intermediate products of formula (IV) obtained according to known processes are unstable and decomposing compounds, which are not only difficult to handle on a technical scale but also are still in the need of an additional purification by recrystallization. According to the known processes the crude intermediate products of formula (IV) are obtained in the form of concentrates by evaporation of the reaction mixture. Generally, the impurities in such concentrates are decomposition products of the crude intermediate products or relatively low molecular substances. It The removal of such foreign substances from the concentrates for isolating the pure intermediate products of formula (IV) has turned out very difficult and rich in losses;
(3) In the known processes for preparing the thiophene derivatives of formula (I) it is necessary to use crystallization processes, which are extremely slow and time consuming in order to obtain pure products on a large technical scale. When the crystallization of the purified solutions obtained is carried out too rapidly, in frequent cases not a crystalline precipitate results, but first a cloudiness and then an oily precipitate, this making a further purification necessary, which in turn decreases the yield in crystalline end product considerably;
(4) Further, the known processes have the disadvantage that some lead to a low yield of 72% at most, and others are connected with difficulties upon application on a large technical scale, require the use of expensive solvents or do not allow direct crystallization.